Studies are being conducted to evaluate the acute and short-term toxicity of arsine gas. Fischer 344 rats, B6C3F1 and C57BL/6 mice, and Syrian golden hamsters have been exposed to arsine gas at concentrations of 10 ppb to 50 ppm for periods ranging from .5 hr to 90 days. All groups exposed to a single 6 hr exposure of 25 ppm experienced 100% mortality, while those exposed to 5 ppm for as long as four weeks or 2.5 ppm for 13 weeks showed no overt signs of toxicity. A dose-dependent increase in spleen weights and a slight increase in liver weights was observed at necropsy. Microscopic examination of spleens from exposed rats showed sequestration of macrophages and increased erythropoiesis. Blood samples showed small decreases in packed cell volume and a marked increase in ALAD activity. Urine samples showed elevated levels of coproporphyrin and 7 and 8 carboxyl uroporphyrin species. The effects on both sexes and all three species were similar. The data suggests that alterations in the heme biosynthetic pathway may be used as early biological indicators of ongoing arsine toxicity. Single exposures to 25 ppm for .5 to 3 hours caused severe loss of circulating RBC's which were observed as early as 8 hours after the initiation of exposure. RBC counts began to recover four days after exposure but had not returned to control values after seven days.